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After administration of tamsulosin to group I the frequency of bladder contractions decreased significantly and the duration of minimal urethral relaxation with high-frequency oscillations (HFOs) was significantly prolonged. Except for mean arterial blood pressure (MAP), none of the variables in group I differed significantly from those in group II and group III. The change in MAP after tamsulosin treatment was significantly lower than after doxazosin or phentolamine. Except for the maximum Pves, which was significantly higher in males (group IV) than in females of group I, the UPP and Pves curves of male rats were similar to those of females before giving tamsulosin. The prolonged frequency and duration of HFO in group IV (with tamsulosin) were significantly different from those of females.
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These data indicate that the alpha 1-adrenoreceptor blockers, naftopidil and doxazosin, inhibit Ca2+ mobilization, this mechanism being possibly the means whereby these drugs inhibit platelet aggregation.
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We analyzed the prescriptions of alpha-blockers and phosphodiesterase 5 inhibitors (PDE5Is) in the urology department as well as in other departments of the general hospital.
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The addition of CKD status and stratification by race does not improve risk prediction in high-risk hypertensive patients.
The effect of nifedipine on pressor dose-response curves to phenylephrine, alpha-methylnoradrenaline and angiotensin II was determined in anaesthetized cats pretreated with propranolol and atropine. The selectivity of phenylephrine and alpha-methylnoradrenaline for postjunctional alpha 1- and alpha 2-adrenoceptors respectively was demonstrated by using the selective alpha 1-adrenoceptor antagonist doxazosin and the relatively selective alpha 2-adrenoceptor antagonist rauwolscine. Nifedipine infused intravenously produced a degree of inhibition of rises in diastolic blood pressure similar to that induced by all three agonists. It is concluded that alpha 1- and alpha 2-adrenoceptor activation induced by phenylethanolamine derivatives is equally dependent on extracellular calcium for vascular smooth muscle contraction. Antagonism of sympathetically mediated or angiotensin-induced vasoconstriction could contribute to the vasodilator effects of nifedipine.
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The study was performed in untreated SHRs (n=16) and SHRs that were orally treated with doxazosin (10 mg/kg body weight per day, for 15 days), a selective alpha1-receptor blocker (n=16). A group of Wistar-Kyoto (WKY) rats (n=16) was used as the control.
Twenty patients with essential hypertension were randomised to a 7-week period of dose titration with doxazosin, 1-8mg/day or enalapril, 5-20mg/day. In a further 7-week period the dosage level reached with the initial drug was halved, and titration with the second agent was carried out. Blood pressure responses at the end of each treatment period were assessed by clinic measurements made 24 hours post-dose. In the first treatment period, enalapril (mean dose 19mg/day) reduced serum free ACE activity by 40% and had a greater effect than doxazosin (mean dose 5.2mg/day) on clinic supine blood pressure (systolic and diastolic). In the second period, the addition of enalapril to doxazosin was associated with a significant fall in clinic standing blood pressure (systolic and diastolic), despite the doxazosin dose reduction and consequent decrease in median plasma doxazosin concentration (from 10.6 to 5.2ng/ml). Alternatively, when doxazosin was added to enalapril, free ACE activity remained 40% decreased despite enalapril dose reduction, and blood pressure was not further affected. Plasma renin activity was increased by enalapril. No changes were observed in plasma aldosterone or lipid concentrations with either drug. The combination of doxazosin and enalapril was well tolerated and lowered blood pressure overall. Judged by clinic measurements 24 hours post-dose, most of the antihypertensive effect was attributable to the enalapril component. However, ambulatory blood pressure monitoring 0-12 hours post-dose in a subset of patients suggested a contribution of doxazosin earlier in the dose interval.
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We studied doxazosin (1-8 mg) and bendrofluazide (2.5 mg) in patients of British South Asian origin with existing mild to moderate hypertension (doxazosin n = 78; bendrofluazide n = 82), to compare their effects on glucose and lipid metabolism in this group.
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This is the first set of studies that reports the novel anti-inflammatory effects of doxazosin.
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ATP-binding cassette transporter A1 (ABCA1) is a rate-limiting factor for high-density lipoprotein (HDL) biogenesis. The ABCA1 gene expression is known to be upregulated by various transcriptional factors. However, negative regulation factors would be better targets for pharmacological modulation of HDL biogenesis. Doxazosin, an alpha(1)-adrenoceptor blocker, increased ABCA1 mRNA, its protein, and apolipoprotein A-I-mediated HDL biogenesis in THP-1 macrophages and CHO-K1 cells, independent of alpha(1)-adrenoceptor blockade. Analysis of the human ABCA1 promoter indicated that the region between the positions -368 and -147 that contains an activator protein (AP)2-binding site responsible for the effects of doxazosin. Overexpression of AP2alpha inhibited ABCA1 transcription in a dose-dependent fashion. Mutation in the AP2-binding site caused increase of the basal promoter activity and cancelling both the transactivation by doxazosin and the trans-repression by AP2alpha. Doxazosin had no effect on ABCA1 mRNA level in HepG2 cells, which lack endogenous AP2alpha, and it reversed the inhibitory effect of AP2alpha expression in this type of cells. Chromatin immunoprecipitation and gel shift assays revealed that doxazosin reduced specific binding of AP2alpha to the ABCA1 promoter, as it suppressed phosphorylation of AP2alpha. Finally, doxazosin increased ABCA1 expression and plasma HDL in mice. We thus concluded that AP2alpha negatively regulates the ABCA1 gene transcription. Doxazosin inhibits AP2alpha activity independent of alpha(1)-adrenoceptor blockade and increases the ABCA1 expression and HDL biogenesis. AP2alpha is a potent pharmacological target for the increase of HDL.
In the future, the number of older men in the US will increase dramatically. Likely the percentage of patients undergoing surgical treatment such as TURP will decrease but the absolute number having surgery will increase. It is also likely that alpha(1)-adrenoceptor antagonists will be used with greater frequency in the future and finasteride will be used less frequently. Copyrightz1999S.KargerAG,Basel
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MEN2 patients with pheochromocytoma, despite their smaller tumors, do not distinguish themselves from non-MEN patients in terms of hypertensive episodes during pheochromocytoma resection. Therefore, pretreatment with α- and β-blockade remains the standard of care in MEN2-related as well as in non-MEN-related pheochromocytomas.
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Alpha-blockers were prescribed to 11,436 patients in total over 3 years, and the total frequency of prescriptions was 68,565. Among other departments, the nephrology department had the highest frequency of prescription of 3,225 (4.7%), followed by the cardiology (3,101, 4.5%), neurology (2,576, 3.8%), endocrinology (2,400, 3.5%), pulmonology (1,102, 1.6%), and family medicine (915, 1.3%) departments in order. PDE5Is were prescribed to 2,854 patients in total over 3 years, and the total frequency of prescriptions was 10,558. The prescription frequency from the urology department was 4,900 (46.4%). Among other departments, the endocrinology department showed the highest prescription frequency of 3,488 (33.0%), followed by the neurology (542, 5.1%), cardiology (467, 4.4%), and family medicine (407, 3.9%) departments in order.
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Baseline subject characteristics were comparable. Thirty subjects entered the study: 8 subjects in DOX-slow, 9 subjects in DOX-fast, and 13 subjects in placebo. Total number of cocaine-negative urines was significantly increased in the DOX-fast group; and percentage of total cocaine-negative urines by group were 10% for DOX-slow group, 35% for DOX-fast group, and 14% for placebo (χ(2)=36.3, df=2, p<0.0001). The percentage of participants achieving two or more consecutive weeks of abstinence by group was 0% for DOX-slow group, 44% for DOX-fast group, and 7% for placebo (χ(2)=7.35, df=2, p<0.023).
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The antihypertensive efficacy, safety, and lipid effects of doxazosin, a selective alpha 1-inhibitor, were assessed in a general practice setting. Three hundred twenty-six patients were entered into the study, which involved three phases: (1) a 2-week baseline period, (2) an 8-week period in which patients received 1 to 8 mg of doxazosin once daily, and (3) a 4-week maintenance period. After 12 weeks, 78.8% of efficacy-evaluable patients were considered therapy successes (sitting diastolic blood pressure either less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction from baseline or greater than or equal to 10 mm Hg reduction from baseline). The mean daily dose in patients considered a therapy success was 2.8 mg. By the final visit, sitting systolic/diastolic blood pressures of these patients were reduced by 16.4/13.5 mm Hg from a mean baseline of 170/106 mm Hg. The investigators' global assessment of efficacy of once-daily doxazosin therapy was excellent or good for 70% of patients. Of the 326 patients, 30.7% reported a total of 160 side effects; 78% of the side effects were mild or moderate in severity, and 24 patients (7.4%) discontinued treatment because of adverse experiences. The investigators' global assessment of toleration was excellent or good for 87% of patients. Doxazosin produced a significant decrease in total cholesterol (p = 0.02) and triglyceride (p less than 0.001) levels. From baseline to final visit there was also a highly significant reduction of 17% (p less than 0.001) in calculated risk score for coronary heart disease on the basis of the Framingham Heart Study risk equation.
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To study the clinical effects of kidney-tonifying and dampness-expelling Chinese herbal medicine combined with doxazosin in the treatment of chronic epididymitis.
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Better knowledge of prevalence and early-stage determinants of subclinical left ventricular dysfunction (LVD) in type 2 diabetes would be useful to design prevention strategies. The objective of the LVD in Diabetes (DYDA) study was to assess these points in patients without established cardiac disease.
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Adult Wistar rats were treated with doxazosin (25mg/kg/day), and the ventral prostates were excised at 7 and 30days after treatment. Untreated rats were controls. Ventral prostates were subjected to ultrastructural, immunohistochemical, biochemical and molecular analyses.
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Collagen (5 microg/ml) stimulation of washed platelets increased endogenous serotonin (5-HT) release to the medium from 13.88 1.39 to 188.67 26.37 pmol/108 platelets ( P < 0.001). Adrenaline (16 microM) also increased 5-HT release, from 11.0 1.46 to 110.6 29.9 pmol/108 platelets ( P < 0.02). Naftopidil enhanced collagen-induced 5-HT efflux; significant increases occurred with 2 microM (+71.6%, P < 0.01), 10 microM (+89.1%, P < 0.01) and 40 microM (+69.7%, P < 0.01). With 0.4 muM and 2 microM naftopidil, adrenaline-induced 5-HT release was enhanced, albeit non-significantly, whilst with 10 microM and 40 muM naftopidil release was reduced (40 microM,-58.5%, P < 0.05). Doxazosin increased collagen-induced 5-HT release, significant increases being recorded with 7.5 microM (+81.7%, P < 0.05) and 30 microM (+78.4%, P < 0.05). Adrenaline-induced 5-HT release was also increased by doxazosin, but not significantly. Collagen-stimulated 5-HT release was inhibited by nifedipine (7 microM,-38.8%, P < 0.05; 28 microM, -61.2%, P < 0.001). These data suggest that the-antagonists, naftopidil and doxazosin, and the Ca2+ channel blocker, nifedipine, influence agonist-induced platelet 5-HT release through different mechanisms. Thus naftopidil and doxazosin may possess 5-HT transporter-blocking activity. The observation that naftopidil inhibited, adrenaline-induced 5-HT release may indicate that naftopidil also inhibits adrenaline uptake and exchange with dense granular 5-HT, with consequent inhibition of 5-HT release and platelet aggregation. The data obtained with nifedipine are consistent with 5-HT release being reduced as a result of its inhibitory action on platelet Ca2+ mobilisation.
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The efficacy and safety of doxazosin treatment for BPH were confirmed in this Asian population. Significant improvements in total IPSS, as well as obstructive and irritative subscores, were observed.